Accurate quantitative descriptions of the interactions of membrane-active proteins and peptides with membrane interfaces is important for understanding many important problems, including how membrane binding domains interact with membranes to target signal transduction proteins to various subcellular compartments, how pH-induced refolding on membranes of the diphtheria toxin T-domain cause highly charged helices to cross lipid bilayers, and how simpler toxins and antimicrobial peptides permeabilize membranes. One of the most challenging aspects of the development of quantitative descriptions is the shortage of structural methods for observing molecular interactions in fluid lipid membranes. The general goal of this research project is the development and exploitation of such methods for interpreting measurements of peptide-bilayer interaction energies at the molecular level. These new methods involve the concerted use of molecular dynamics simulations and x-ray & neutron diffraction measurements to obtain dynamic structural images of peptide-bilayer interactions in thermally disordered membranes. Our specific aims are to (1) advance the development of a novel diffraction method--Molecular Dynamics/Absolute Scale (MoDAS) refinement--in order to gain dynamic structural images of peptides interacting at the atomic level with thermally disordered lipid bilayers, (2) clarify how hydrophobic and electrostatic interactions work together at membrane interfaces to mediate protein-lipid interactions, (3) improve physicochemical rules for predicting the binding and folding of peptides at membrane interfaces by establishing a structural context for them, and (4) use neutron diffraction experiments, quantum chemical calculations, and MD simulations to gain insights into the preference of tryptophan side chains for the membrane interface. [unreadable] [unreadable]